The overall objective of the proposed research program is to throw more light on the molecular and physiological interrelationships between stimulus-receptor interaction and polyphosphoinositide turnover at the neuromuscular junction of the iris smooth muscle. In previous communications from this laboratory, we reported that phosphoinositides mediate alpha-adrenergic and cholinergic muscariuic receptor function via Ca2 ions in the iris. In the coming year, we plan to marshal further experimental evidence in support of this hypothesis through studies on the release of inositol phosphates in response to cholinergic and adrenergic stimuli. The effects of Ca2 ion and Ca2 ion antagonistis such as verapamil, dibenamine and lanthanum on the release of these water-soluble products will also be investigated. Furthermore, binding studies using radioligands such as (3H) ONB, (3H) WB4101 and (3H) DHE will be employed to characterize the cholinergic and alpha-adrenergic receptors of the iris. The kinetic coustants obtained with this method will be compared with those obtained previously from this laboratory with the biochemical and pharmaclogical methods.